The prostate gland, which is found exclusively in male mammals, produces several components of semen and blood and several regulatory peptides. The prostate gland comprises stroma and epithelium cells, the latter group consisting of columnar secretory cells and basal nonsecretory cells. A proliferation of these basal cells as well as stroma cells gives rise to benign prostatic hyperplasia (BPH) which is one common prostate disease. Another common prostate disease is prostatic adenocarcinoma (CaP) which is the most common of the fatal pathophysiological prostate cancers and involves a malignant transformation of epithelial cells in the peripheral region of the prostate gland. Prostatic adenocarcinoma and benign prostatic hyperplasia are two common prostate diseases which have a high rate of incidence in the aging human male population. Approximately one out of every four males above the age of 55 suffers from a prostate disease of some form or another. Prostate cancer is the second most common cause of cancer related death in elderly men with there being approximately 96,000 cases diagnosed and about 26,000 deaths reported annually in the United States.
Studies of the various substances synthesized and secreted by normal, benign and cancerous prostates carried out in order to gain an understanding of the pathogenesis of the various prostate diseases reveal that certain of these substances may be used as immunohistochemical tumour markers in the diagnosis of prostate disease. The three predominant proteins or peptides secreted by a normal prostate gland are Prostatic Acid Phosphatase (PAP), Prostate Specific Antigen (PSA) and prostatic inhibin (PIP) also known as human seminal plasma inhibin (HSPI) and hereinafter referred to as HSPI.
Metabolic and immunohistochemical studies have shown that the prostate is a major source of HSPI. HSPI is involved in the feedback control of, and acts to suppress secretion of, circulating follicle stimulating hormone (FSH) both in-vitro and in-vivo in adult male rats. HSPI acts both at the pituitary as well as at the prostate site since both are provided with receptor sites for HSPI.
Both PSA and PAP have been studied as tumour markers in the detection of prostate disease but since both exhibit elevated levels in prostates having benign prostatic hyperplasia (BPM) neither marker is specific and therefore they are of limited utility.
Recently, it has been shown that HSPI concentrations in serum of patients with BPH or CaP are significantly higher than normal. The highest serum concentration of HSPI observed in normal men is approximately 40 ng/ml., while in men with either BPH or CaP serum concentrations of HSPI have been observed in the range from 300-400 ng/ml. Because there exists some overlap in the concentrations of HSPI in subjects having normal prostates and patients exhibiting either BPH or CaP, serum levels in and of themselves are of little value.
A major therapy in the treatment of prostate cancer is androgen-ablation. While most patients respond initially to this treatment, its effectiveness decreases over time possibly because of the presence of a heterogenous population of androgen-dependant and androgen-independent cells to begin with. In such a scenario, the androgen sensitive cells respond to the androgen treatment while any androgen insensitive cells present would continue to proliferate unabated.
Other forms of cancer which are currently exacting a heavy toll are breast cancer in women and cancer of the gastrointestinal tract. Currently, the use of various cancer drugs such as mitomycin, idarubicin, cisplatin, 5-flouro-uracil, methotrexate, adriamycin and donomycin form part of the therapy for treating such cancers. One drawback to such a therapeutic treatment is the presence of adverse side effects due to the drugs in the concentration ranges required for effective treatment.
Accordingly, it would be advantageous to find a more effective means of arresting the growth of prostate, breast and gastrointestinal cancer cells and tumours which can be used effectively against both androgen sensitive and androgen insensitive cells.